The roles of microRNAs and protein components of the microRNA pathway in lung development and diseases.

Decades of studies have shown evolutionarily conserved molecular networks consisting of transcriptional factors, diffusing growth factors, and signaling pathways that regulate proper lung development. Recently, microRNAs (miRNAs), small, noncoding regulatory RNAs, have been integrated into these networks. Significant advances have been made in characterizing the developmental stage- or cell type-specific miRNAs during lung development by using approaches such as genome-wide profiling and in situ hybridization. Results from gain- or loss-of-function studies revealed pivotal roles of protein components of the miRNA pathway and individual miRNAs in regulating proliferation, apoptosis, differentiation, and morphogenesis during lung development. Aberrant expression or functions of these components have been associated with pulmonary disorders, suggesting their involvement in pathogenesis of these diseases. Moreover, genetically modified mice generated in these studies have become useful models of human lung diseases. Challenges in this field include characterization of collective function and responsible targets of miRNAs specifically expressed during lung development, and translation of these basic findings into clinically relevant information for better understanding of human diseases. The goal of this review is to discuss the recent progress on the understanding of how the miRNA pathway regulates lung development, how dysregulation of miRNA activities contributes to pathogenesis of related pulmonary diseases, and to identify relevant questions and future directions.